This review discusses the role of brain-derived neurotrophic factor (BDNF) in activity-dependent synaptic modulation. It highlights how neuronal activity regulates BDNF gene transcription, mRNA transport, and protein secretion, as well as the trafficking of the BDNF receptor, TrkB. The review emphasizes that BDNF can mediate synaptic plasticity in a local and synapse-specific manner through various mechanisms, including activity-dependent transcription, local translation, and secretion. It also discusses how BDNF can act preferentially on active synapses, possibly through activity-dependent control of synaptic responsiveness to BDNF. The review further explores the mechanisms by which BDNF can be restricted to active synapses, such as activity-dependent transcription, local secretion, and receptor trafficking. The review concludes that understanding how neurotrophins can mediate activity-dependent plasticity in a local and synapse-specific manner is an important direction for future research.This review discusses the role of brain-derived neurotrophic factor (BDNF) in activity-dependent synaptic modulation. It highlights how neuronal activity regulates BDNF gene transcription, mRNA transport, and protein secretion, as well as the trafficking of the BDNF receptor, TrkB. The review emphasizes that BDNF can mediate synaptic plasticity in a local and synapse-specific manner through various mechanisms, including activity-dependent transcription, local translation, and secretion. It also discusses how BDNF can act preferentially on active synapses, possibly through activity-dependent control of synaptic responsiveness to BDNF. The review further explores the mechanisms by which BDNF can be restricted to active synapses, such as activity-dependent transcription, local secretion, and receptor trafficking. The review concludes that understanding how neurotrophins can mediate activity-dependent plasticity in a local and synapse-specific manner is an important direction for future research.